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-Structure paper
タイトル | Structures of LRP2 reveal a molecular machine for endocytosis. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 4, Page 821-836.e13, Year 2023 |
掲載日 | 2023年2月16日 |
![]() | Andrew Beenken / Gabriele Cerutti / Julia Brasch / Yicheng Guo / Zizhang Sheng / Hediye Erdjument-Bromage / Zainab Aziz / Shelief Y Robbins-Juarez / Estefania Y Chavez / Goran Ahlsen / Phinikoula S Katsamba / Thomas A Neubert / Anthony W P Fitzpatrick / Jonathan Barasch / Lawrence Shapiro / ![]() |
PubMed 要旨 | The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in ...The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2 or megalin) is representative of the phylogenetically conserved subfamily of giant LDL receptor-related proteins, which function in endocytosis and are implicated in diseases of the kidney and brain. Here, we report high-resolution cryoelectron microscopy structures of LRP2 isolated from mouse kidney, at extracellular and endosomal pH. The structures reveal LRP2 to be a molecular machine that adopts a conformation for ligand binding at the cell surface and for ligand shedding in the endosome. LRP2 forms a homodimer, the conformational transformation of which is governed by pH-sensitive sites at both homodimer and intra-protomer interfaces. A subset of LRP2 deleterious missense variants in humans appears to impair homodimer assembly. These observations lay the foundation for further understanding the function and mechanism of LDL receptors and implicate homodimerization as a conserved feature of the LRP receptor subfamily. |
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手法 | EM (単粒子) |
解像度 | 2.8 - 3.3 Å |
構造データ | EMDB-28233, PDB-8em4: EMDB-28241, PDB-8em7: ![]() EMDB-28242: Local refinement map of LRP2 P1-P2 domains at pH 7.5 ![]() EMDB-28243: Local refinement of P3-P6 domains of LRP2 at pH 7.5 ![]() EMDB-28250: Local refinement of the P7 domain of LRP2 at pH 7.5 ![]() EMDB-28251: Local refinement of the R4 domain of LRP2 at pH 7.5 ![]() EMDB-28252: Local refinement of P8 domain of LRP2 at pH 7.5 ![]() EMDB-28253: Local refinement of P1-P2 domains of LRP2 at pH 5.2 ![]() EMDB-28258: Local refinement of P3-P6 domains of LRP2 at pH 5.2 ![]() EMDB-28260: Local refinement of P7 domain of LRP2 at pH 5.2 ![]() EMDB-28261: Local refinement of R3 domain of LRP2 at pH 5.2 ![]() EMDB-28265: Local refinement of P8 domain of LRP2 at pH 5.2 |
化合物 | ![]() ChemComp-NGA: ![]() ChemComp-NAG: ![]() ChemComp-CA: |
由来 |
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![]() | MEMBRANE PROTEIN / LRP2 / Megalin / GP330 / Endocytosis |